Granulomas are dynamic, focal, inflammatory, tissue-destructive reactions to persistent tissue irritants which involve intricate cell-cell interactions. The initial premise of this project is that granulomas of the gut are subject to immunoregulation by cells from gut associated lymphoid tissue (GALT) and that Crohn's disease may be the consequence of a defect in this immunoregulatory process. The objectives of this investigation are to study the intestinal response to granulomatous stimuli in murine schistosomiasis and Crohn's disease and to analyze immunoregulatory mechanisms and cellular interactions occurring during evolution of these intestinal lesions. RESEARCH OBJECTIVES: Murine Schistosomiasis - I. Quantitate differences between liver, colon, and ileal granulomas by determining cellular composition and assaying for lymphokine production. II. Determine if GALT governs modulation of liver or intestinal granulomas by using adoptive transfer experiments and measuring granuloma size and spleen cell MIF production. Crohn's Disease - I. Isolate intestinal granuloma and determine if the intestinal granuloma of Crohn's disease is a delayed hypersensitivity response by assaying for spontaneous MIF production. Understanding these processes may provide insight into the etiology of inflammatory bowel disease and improve therapeutic modalities.